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Trial Title: A Study of Efficacy and Safety of Pembrolizumab Plus Enfortumab Vedotin (EV) +/- Investigational Agents in First-Line Metastatic Urothelial Carcinoma (mUC) (MK-3475-04B/KEYMAKER-U04)

NCT ID: NCT05845814

Condition: Metastatic Urothelial Carcinoma
Urothelial Neoplasms

Conditions: Official terms:
Carcinoma
Carcinoma, Transitional Cell
Pembrolizumab

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Active, not recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: In Part 1, participants will be randomized in a 1:1:1 ratio to receive either Arm A (coformulated favezelimab/pembrolizumab plus EV), Arm B (coformulated vibostolimab/pembrolizumab plus EV), or Arm C (pembrolizumab plus EV). If Part 2 is conducted, participants will be randomized in a 1:1:1 ratio to Arms A, B, and C or in a 1:1 ratio to Arms A and C or B and C, depending on the treatment arm(s) that are expanded in Part 2.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: Coformulated favezelimab/pembrolizumab
Description: Coformulated favezelimab/pembrolizumab (800 mg/200 mg) IV infusion
Arm group label: Arm A: Coformulated favezelimab/pembrolizumab plus EV

Other name: MK-4280A

Intervention type: Biological
Intervention name: Coformulated vibostolimab/pembrolizumab
Description: Coformulated vibostolimab/pembrolizumab (200 mg/200 mg) IV infusion
Arm group label: Arm B: Coformulated vibostolimab/pembrolizumab plus EV

Other name: MK-7684A

Intervention type: Combination Product
Intervention name: EV
Description: 1.25 mg/kg IV infusion
Arm group label: Arm A: Coformulated favezelimab/pembrolizumab plus EV
Arm group label: Arm B: Coformulated vibostolimab/pembrolizumab plus EV
Arm group label: Arm C: Pembrolizumab plus EV

Other name: Padcev

Other name: ASG-22CE

Other name: ASG-22ME

Intervention type: Biological
Intervention name: Pembrolizumab
Description: 200 mg IV infusion
Arm group label: Arm C: Pembrolizumab plus EV

Other name: MK-3475

Other name: KEYTRUDA®

Summary: This study is a substudy being conducted under one pembrolizumab umbrella master study KEYMAKER-U04. The substudy will consist of 2 parts. Part 1 will evaluate the efficacy and safety of coformulated favezelimab/pembrolizumab plus EV and coformulated vibostolimab/pembrolizumab plus EV relative to pembrolizumab plus EV. There will be no comparison of coformulated favezelimab/pembrolizumab plus EV versus coformulated vibostolimab/pembrolizumab plus EV. If ORR and/or DRR are substantially better on coformulated favezelimab/pembrolizumab plus EV and/or coformulated vibostolimab/pembrolizumab plus EV compared with pembrolizumab plus EV, after evaluation of the totality of data, the sponsor might consider Part 2 (expansion) to further characterize the efficacy and safety of the treatment arms under study.

Detailed description: The master study for this substudy is MK-3475-U04/KEYMAKER-U04. The master study will not be screening any participants and will not be registered.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Must have histologically documented, locally advanced/metastatic urothelial carcinoma (la/mUC). - Participants with mixed histology are eligible provided the urothelial component is ≥50% (and <10% plasmacytoid component) - Participants whose tumors contain any neuroendocrine component are not eligible (variant histology to be confirmed locally) - Must not have received prior systemic therapy for la/mUC. The following therapies in earlier disease setting (eg, muscle-invasive urothelial carcinoma (MIUC)) are permitted: - Participants that received neoadjuvant or adjuvant chemotherapy are permitted. - Participants who received anti- programmed cell death 1 protein (PD-1) or programmed cell death ligand 1 (PD-L1) therapy for an earlier disease stage (eg, NMIBC, MIUC) with progression/recurrence >12 months from completion of therapy are permitted. - Must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequate for biomarker evaluation. A newly obtained biopsy is strongly preferred, but not required if archival tissue is evaluable. - Any AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Endocrine-related AEs adequately treated with hormone replacement or with

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Moores Cancer Center ( Site 3028)

Address:
City: La Jolla
Zip: 92093
Country: United States

Facility:
Name: University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 3045)

Address:
City: Orange
Zip: 92868
Country: United States

Facility:
Name: Anschutz Cancer Pavilion ( Site 3017)

Address:
City: Aurora
Zip: 80045
Country: United States

Facility:
Name: Emory University School of Medicine ( Site 3043)

Address:
City: Atlanta
Zip: 30322
Country: United States

Facility:
Name: Indiana University Melvin and Bren Simon Cancer Center ( Site 3011)

Address:
City: Indianapolis
Zip: 46202
Country: United States

Facility:
Name: Washington University School of Medicine ( Site 3038)

Address:
City: Saint Louis
Zip: 63110
Country: United States

Facility:
Name: Icahn School of Medicine at Mount Sinai ( Site 3018)

Address:
City: New York
Zip: 10029
Country: United States

Facility:
Name: Memorial Sloan Kettering Cancer Center ( Site 3031)

Address:
City: New York
Zip: 10065
Country: United States

Facility:
Name: Cleveland Clinic-Taussig Cancer Center ( Site 3036)

Address:
City: Cleveland
Zip: 44195
Country: United States

Facility:
Name: UPMC Hillman Cancer Center ( Site 3014)

Address:
City: Pittsburgh
Zip: 15232
Country: United States

Facility:
Name: Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 3041)

Address:
City: Salt Lake City
Zip: 84112
Country: United States

Facility:
Name: Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si

Address:
City: Brisbane
Zip: 4029
Country: Australia

Facility:
Name: Austin Health-Cancer Clinical Trials Centre ( Site 3950)

Address:
City: Heidelberg
Zip: 3084
Country: Australia

Facility:
Name: The Ottawa Hospital - General Campus-The Ottawa Hospital Cancer Centre ( Site 3105)

Address:
City: Ottawa
Zip: K1H 8L6
Country: Canada

Facility:
Name: Sunnybrook Research Institute - Odette Cancer Centre ( Site 3108)

Address:
City: Toronto
Zip: M4N 3M5
Country: Canada

Facility:
Name: Princess Margaret Cancer Centre ( Site 3106)

Address:
City: Toronto
Zip: M5G 2M9
Country: Canada

Facility:
Name: FALP-UIDO ( Site 3151)

Address:
City: Santiago
Zip: 7500921
Country: Chile

Facility:
Name: Bradfordhill-Clinical Area ( Site 3155)

Address:
City: Santiago
Zip: 8420383
Country: Chile

Facility:
Name: ONCOCENTRO APYS-ACEREY ( Site 3158)

Address:
City: Viña del Mar
Zip: 2520598
Country: Chile

Facility:
Name: Bradford Hill Norte ( Site 3152)

Address:
City: Antofagasta
Zip: 1240000
Country: Chile

Facility:
Name: CHU de Bordeaux Hop St ANDRE ( Site 3607)

Address:
City: Bordeaux
Zip: 33075
Country: France

Facility:
Name: Centre Georges François Leclerc-Centre de recherche clinique ( Site 3608)

Address:
City: Dijon
Zip: 21079
Country: France

Facility:
Name: Oncopole Claudius Regaud ( Site 3610)

Address:
City: Toulouse
Zip: 31059
Country: France

Facility:
Name: Hôpital Européen Georges Pompidou ( Site 3605)

Address:
City: Paris
Zip: 75015
Country: France

Facility:
Name: centre hospitalier lyon sud ( Site 3606)

Address:
City: Pierre-Bénite
Zip: 69310
Country: France

Facility:
Name: Rambam Health Care Campus-Oncology Division ( Site 3501)

Address:
City: Haifa
Zip: 3109601
Country: Israel

Facility:
Name: Rabin Medical Center-Oncology ( Site 3504)

Address:
City: Petah Tikva
Zip: 4941492
Country: Israel

Facility:
Name: Sheba Medical Center-ONCOLOGY ( Site 3503)

Address:
City: Ramat Gan
Zip: 5265601
Country: Israel

Facility:
Name: Ospedale San Raffaele-Oncologia Medica ( Site 3403)

Address:
City: Milano
Zip: 20132
Country: Italy

Facility:
Name: Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 3405)

Address:
City: Milan
Zip: 20133
Country: Italy

Facility:
Name: Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 3406)

Address:
City: Napoli
Zip: 80131
Country: Italy

Facility:
Name: Severance Hospital, Yonsei University Health System-Medical oncology ( Site 3903)

Address:
City: Seoul
Zip: 03722
Country: Korea, Republic of

Facility:
Name: Asan Medical Center-Department of Oncology ( Site 3901)

Address:
City: Seoul
Zip: 05505
Country: Korea, Republic of

Facility:
Name: Samsung Medical Center ( Site 3902)

Address:
City: Seoul
Zip: 06351
Country: Korea, Republic of

Facility:
Name: Maastricht UMC+ ( Site 3304)

Address:
City: Maastricht
Zip: 6229 HX
Country: Netherlands

Facility:
Name: Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)-medical oncology ( Site 3302)

Address:
City: Amsterdam
Zip: 1066 CX
Country: Netherlands

Facility:
Name: Erasmus Medisch Centrum-Medical Oncology ( Site 3303)

Address:
City: Rotterdam
Zip: 3015 GD
Country: Netherlands

Facility:
Name: Hospital Universitari Vall d'Hebron ( Site 3767)

Address:
City: Barcelona
Zip: 08035
Country: Spain

Facility:
Name: Hospital Clinico San Carlos ( Site 3765)

Address:
City: Madrid
Zip: 28040
Country: Spain

Facility:
Name: Chang Gung Memorial Hospital at Kaohsiung-Oncology and Hematology ( Site 3802)

Address:
City: Kaohsiung
Zip: 83301
Country: Taiwan

Facility:
Name: National Cheng Kung University Hospital-Clinical Trial Center ( Site 3803)

Address:
City: Tainan
Zip: 704
Country: Taiwan

Facility:
Name: National Taiwan University Hospital-Oncology ( Site 3801)

Address:
City: Taipei
Zip: 10002
Country: Taiwan

Facility:
Name: St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 3206)

Address:
City: London
Zip: EC1A 7BE
Country: United Kingdom

Facility:
Name: ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 3201)

Address:
City: London
Zip: SW3 6JJ
Country: United Kingdom

Start date: June 23, 2023

Completion date: May 31, 2027

Lead sponsor:
Agency: Merck Sharp & Dohme LLC
Agency class: Industry

Source: Merck Sharp & Dohme LLC

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05845814
https://www.merckclinicaltrials.com/
https://trialstransparency.merckclinicaltrials.com/Study.aspx?id=3475-04B&&kw=3475-04B

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